Thyroid hormone differentially augments biliary sterol secretion in the rat. I. The isolated-perfused liver model

Thyroid hormone lowers serum cholesterol and alters sterol metabolic processes. This laboratory has previously reported increased biliary lipid secretion as an early effect of triiodothyronine (T₃) in the rat. To evaluate whether the bile lipid action of T₃ is a primary or secondary effect, the isolated-perfused rat liver model was used. Red blood cells in lipid-free buffer were used to perfuse livers of euthyroid and methimazole- hypothyroid rats, as well as hypothyroid rats given T₃ at intervals before perfusion. Bile flow was maintained by taurocholate perfusion. Hypothyroid rats had elevated pre-perfusion serum cholesterol compared to euthyroid (107 ± 4 vs. 65 ± 2 mg/dl) and decreased biliary cholesterol (0.016 ± 0.001 vs. 0.031 ± 0.004 μmol/g liver/h) secretion. Serum cholesterol decreased to euthyroid levels by 18 h after T₃, an effect that was prevented by bile duct ligation. Bile cholesterol secretion doubled by 18 h, and reached levels twice euthyroid by 42 h, while phospholipid secretion doubled to levels just above euthyroid. The fourfold increase in biliary cholesterol secretion occurred with lipid-free perfusion and unchanging bile acid uptake or output. It occurred without a fall in hepatic lipoprotein cholesterol secretion. Blockade of cholesterol synthesis with lovastatin failed to alter T₃- augmented bile cholesterol secretion. We conclude that T₃ induces biliary cholesterol secretion concomitantly with the fall in serum cholesterol. This augmented biliary secretion did not appear to depend upon lipoprotein uptake, increased bile acid transport, or cholesterol synthesis. It did not occur at the expense of hepatic lipoprotein secretion. Facilitated biliary lipid secretion may be a primary effect of T₃.